Integrating clinical and genetic approaches in the diagnosis of 46,XY disorders of sex development.

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Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_5A42F47DF7FB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Integrating clinical and genetic approaches in the diagnosis of 46,XY disorders of sex development.
Journal
Endocrine connections
Author(s)
Kolesinska Z., Acierno J., Ahmed S.F., Xu C., Kapczuk K., Skorczyk-Werner A., Mikos H., Rojek A., Massouras A., Krawczynski M.R., Pitteloud N., Niedziela M.
ISSN
2049-3614 (Print)
ISSN-L
2049-3614
Publication state
Published
Issued date
12/2018
Peer-reviewed
Oui
Volume
7
Number
12
Pages
1480-1490
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
46,XY differences and/or disorders of sex development (DSD) are clinically and genetically heterogeneous conditions. Although complete androgen insensitivity syndrome has a strong genotype-phenotype correlation, the other types of 46,XY DSD are less well defined, and thus, the precise diagnosis is challenging. This study focused on comparing the relationship between clinical assessment and genetic findings in a cohort of well-phenotyped patients with 46,XY DSD. The study was an analysis of clinical investigations followed by genetic testing performed on 35 patients presenting to a single center. The clinical assessment included external masculinization score (EMS), endocrine profiling and radiological evaluation. Array-comparative genomic hybridization (array-CGH) and sequencing of DSD-related genes were performed. Using an integrated approach, reaching the definitive diagnosis was possible in 12 children. The correlation between clinical and genetic findings was higher in patients with a more severe phenotype (median EMS 2.5 vs 6; P = 0.04). However, in 13 children, at least one variant of uncertain significance was identified, and most times this variant did not correspond to the original clinical diagnosis. In three patients, the genetic studies guided further clinical assessment which resulted in a reclassification of initial clinical diagnosis. Furthermore, we identified eight patients harboring variants in more than one DSD genes, which was not seen in controls (2.5%; P = 0.0003). In summary, taking into account potential challenges in reaching the definitive diagnosis in 46,XY DSD, only integrated approach seems to be the best routine practice.
Keywords
46,XY DSD, array-comparative genomic hybridization, differences and/or disorders of sex development, massive parallel/next generation sequencing, oligogenicity
Pubmed
Web of science
Open Access
Yes
Create date
13/12/2018 17:36
Last modification date
10/12/2019 7:17
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